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H Martens

Publications and source records attributed to H Martens.

At least 55 records · Page 3Linked to original sources
PubMed1998

Cellular and molecular aspects of thymic T-cell education in neuroendocrine self principles. Implications for autoimmunity.

Thymic epithelial and nurse cells from different species express a repertoire of neuroendocrine polypeptide precursors. This repertoire exerts a dual role in T-lymphocyte selection according to their status either as cryptocrine signals or as neuroendocrine self-antigens of the peptide sequences that are processed from those precursors then presented to pre-T cells. Thymic neuroendocrine self-antigens correspond to peptide sequences highly conserved throughout evolution of their family. Though thymic MHC class I molecules are involved in the processing of thymic neuroendocrine self-antigens, preliminary data show that their presentation to pre-T cells is not allelically restricted. Thymic T-cell education in neuroendocrine families also implies that the structure of a given family may be presented to pre-T cells. Our studies have evidenced the homology between thymic neuroendocrine-related self-antigens and dominant T-cell epitopes of peripheral neuroendocrine signals (neuroendocrine autoantigens). The biochemical difference between neuroendocrine autoantigens and homologous thymic self-antigens might explain the opposite immune responses evoked by those two types of antigens (activation and memory induction vs. tolerogenic effect). Altogether, these studies support the therapeutic use of thymic neuroendocrine self-antigens in reprogramming the immunological self-tolerance that is broken in autoimmune endocrine diseases like insulin-dependent diabetes type I. As recently stated by P. M. Allen in an important review, the fate of developing T lymphocytes in the thymus is influenced by the numerous types of peptidic interactions within the thymic cellular environment. To define the precise nature of thymic cells and naturally occurring biochemical peptide signals involved in positive and negative selection of immature T cells has become a prominent objective for the future research efforts in thymic physiology. This paper will try to show how thymic neuroendocrine-related peptides synthesized and processed within the thymic microenvironment indeed can play a role both in the development of the peripheral T-cell repertoire and in the death of randomly rearranged, self-reactive T cells.

Animals↗
PubMed1998

Effects of dexamethasone on the profile of cytokine secretion in human whole blood cell cultures.

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit the immune and inflammatory responses and are used as immunosuppressive drugs in many inflammatory, autoimmune and allergic diseases. The aims of this study were to investigate the effects of dexamethasone on the profile of cytokine secretion in whole blood cell cultures from healthy subjects and to analyse the gender-related sensitivity to dexamethasone on each cytokine secretion. RESULTS: There was a significant inhibition by dexamethasone (from 1 to 100 nM) on the secretion of monokines (IL-1beta, IL-6, IL-8 and TNF alpha) and lymphokines (IL-2, IL-4, IL-10 and IFN gamma), either after LPS or PHA stimulation (P < 0.01). Interleukin 4 and IL-10 were less inhibited than IFN gamma (P < 0.05 at 1 nM, P < 0.01 at 10 nM and P < 0.001 from 100 nM to 10 microM). No gender difference was observed in the rate of inhibition of the secretion of each cytokine. CONCLUSION: This study shows that the inhibition of cytokine secretion by dexamethasone is more marked on Th1-type cytokines than on Th2-type cytokines. These data support the idea that glucocorticoids may induce a shift from the Th1 to Th2 profile of cytokine secretion.

Adult↗
PubMed1998

Effects of short chain fatty acids and carbon dioxide on magnesium transport across sheep rumen epithelium.

Short chain fatty acids (SCFAs) and CO2 have been shown to stimulate net Mg2+ efflux from the isolated reticulorumen in vivo. To investigate the underlying mechanisms of Mg2+ transport we performed Ussing chamber and microelectrode experiments and measured 28Mg2+ fluxes across sheep rumen epithelium in vitro. In the presence of SCFAs mucosal-to-serosal Mg2+ flux (Jm-sMg) amounted to 82.3 +/- 7.8 nmol cm-2 h-1 and serosal-to-mucosal Mg2+ flux (Js-mMg) to 3.2 +/- 0.7 nmol cm-2 h-1. Replacing SCFAs with gluconate caused a 50% reduction of Jm-sMg, whereas Js-mMg was not affected. Among the SCFAs, n-butyrate was more effective in stimulating Jm-sMg than acetate, propionate or iso-butyrate. Eliminating HCO3(-)-CO2 from SCFA-containing solutions did not affect Mg2+ fluxes, whereas the same replacement in SCFA-free solutions led to a further reduction in Jm-sMg. Jm-sMg decreased after the addition of ethoxyzolamide to SCFA-free, bicarbonate buffered solutions. Decreasing mucosal pH from 6.4 to 5.4 increased Jm-sMg in SCFA-free, bicarbonate buffered solutions. SCFAs had no effect on the apical membrane potential of rumen epithelial cells. The experiments show that both SCFAs and CO2 stimulate Mg2+ transport through an increase in Jm-sMg, most probably via stimulation of a Mg(2+)-2H+ exchange mechanism. SCFAs may have additional metabolic effects on Mg2+ transport.

Animals↗
PubMed1998

Neurohypophysial peptides stimulate the phosphorylation of pre-T cell focal adhesion kinases.

Thymic oxytocin (OT) behaves as a cryptocrine signal targeted at the outer surface of thymic epithelial cell plasma membrane from where OT is able to interact with neurohypophysial peptide receptors expressed by pre-T cells. Immature T cells bear a receptor of the V1 subtype, while OT receptors are predominantly expressed by cytotoxic CD8+ lymphocytes. In both T cell types, neurohypophysial peptide receptors transduce OT via the phosphoinositide pathway. Protein tyrosine phosphorylation is an early event of T cell activation. Western blots of murine pre-T cells (RL12-NP line) proteins probed with anti-phosphotyrosine (PY-20) revealed a great number of proteins the phosphorylation of which increased either with OT or vasopressin treatment. Two were immunoprecipitated with anti-focal adhesion kinase (FAK) mAb 2A7 and were identified one as p125FAK and the other as a coprecipitating 130-kDa protein. The p125FAK is connected to the Ras/MAPK pathway and is also implicated in TCR/CD3 signalling in T cell. Another protein phosphorylated by OT in RL12-NP was identified as paxillin, a 68-kDa protein localised at focal adhesion sites and associated with p 125FAK. These results indicate that phosphorylation of focal adhesion kinase may be induced in pre-T cell by thymic OT.

Animals↗
PubMed1998

Magnesium absorption by wethers fed potassium bicarbonate in combination with different dietary magnesium concentrations.

We hypothesized that the decrease in the absolute amount of Mg absorbed in the total digestive tract, as induced by K, would remain constant if Mg intake by ruminants was increased. This hypothesis was based on earlier studies that used temporarily isolated rumens of sheep and the fact that the rumen is the major site of Mg absorption in ruminants. To test the hypothesis, six rumen-fistulated wethers were fed diets at two concentrations of K and three concentrations of Mg in a 6 x 6 Latin square design. Diets contained either 10 or 36 g of K/kg of dry matter and 1.3, 2.5, or 3.7 g of Mg/kg of dry matter. Extra K was added in the form of KHCO3, and Mg was added in the form of MgO. For wethers fed the low K diets, absolute Mg absorption rose by 0.32 g/d for each 1 g/d of Mg intake that was in excess of requirements. The high K diets reduced absolute Mg absorption by a mean of 0.36 g/d; this reduction was independent of Mg intake. Magnesium intake and Mg concentrations in rumen liquid were positively related. Extra KHCO3 in the diet increased K concentrations in rumen liquid, but the concentrations of Mg remained unchanged. Rumen pH was elevated by a mean of 0.45 units when the high K diets were fed. This study indicated that, in practical ruminant feeding, the supplementation of Mg to either low or high K diets increased absolute Mg absorption to the same extent.

Absorption↗
PubMed1998

[Diphtheria protection in the population of Mecklenburg-Vorpommern].

Evaluation of the diphtheria protection in 764 healthy volunteers before and after the vaccination showed that 56.3% had a reliable immunity, 22.8% a doubtful and 20.9% had no immunity. A high risk is in the age group 41-50 years. Young medical personal and alcoholics also have insufficient diphtheria immunity. The results of 41 healthy volunteers with a basic immunisation of more than 10 years ago prove that one booster shot is sufficient irrespective of the moment of the last vaccination.

Adult↗
PubMed1997

Identification of neurotensin-related peptides in human thymic epithelial cell membranes and relationship with major histocompatibility complex class I molecules.

This study shows the expression at the cell surface of human thymic epithelial cells (TEC) of a neurotensin (NT)-like immunoreactivity. NT radio-immunoassay (RIA) revealed that cultured human TEC contain +/-5 ng immunoreactive (ir) NT/10(6) cells, of which 5% is associated with plasma cell membranes. HPLC analysis of NT-ir present in human TEC showed a major peak of NT-ir corresponding to NT1-13. NT-ir was not detected in the supernatant of human TEC cultures. Using an affinity column prepared with a anti-MHC class I monoclonal antibody, NT-ir-related peptides were retained on the column and eluted together with MHC class I-related proteins. According to the elution time on HPLC of these peptides, they correspond to intact NT1-13, as well as to smaller fragments of NT1-13.

Cell Membrane↗
PubMed1997

Anti-Borrelia burgdorferi immunoglobulin seroprevalence in pulmonary sarcoidosis: a negative report.

The aetiology of sarcoidosis is still unknown. An infectious microorganism as causal agent for this disease could not be identified, but high titres of antibodies against Borrelia burgdorferi were detected in Chinese studies implying a causality with this disease. These findings, however, could not be reproduced by other researchers. The aim of this study was, therefore, to evaluate the possible role of these spirochetes in the pathogenesis of sarcoidosis by serological examinations. Sixty sera of patients suffering from sarcoidosis were examined for anti-B. burgdorferi immunoglobulin by enzyme-linked immunosorbent assay (ELISA). ELISAs for these antibodies show a high sensitivity, but a low specificity; therefore, a specific immunoblot was used to confirm positive results. Initially, 8% of the patients were reactive in the ELISA, and 20% of these could be confirmed by immunoblot. Therefore, the prevalence for B. burgdorferi antibodies in sarcoidosis patients was 1.6%. This result did not differ significantly from the prevalence of B. burgdorferi antibodies in 1,000 regular blood donors of the city of Hamburg (7% reactive in the ELISA, 38% confirmed via immunoblot, prevalence 2.7%). The hypothesis of causality between a B. burgdorferi infection and sarcoidosis cannot be confirmed by this data.

Antibodies, Bacterial↗
PubMed1997

[Physiology and physiopathology of ryanodine receptors in swine. Significance of sensitivity to stress, stress myopathies, malignant hyperthermia and meat quality].

During the last decades intensive breeding of pigs has improved the growth rate, food conversion and the ratio between meat and fat. However, this improvement is very often associated in certain breeds of pig with the porcine stress syndrome, a higher incidence of muscle diseases and a reduced meat quality referred to as pale, soft exudative pork (PSE). These problems are well known since decades and are obviously caused by a variety of factors. The discovery of a mutation in the ryanodine receptor or Ca-release channel in the striated muscles of affected pigs has concentrated research on the function of this protein. The mutation of the ryanodine receptor or Ca-release channel may account for the problems mentioned above because the changed ryanodine receptor can be activated much easier and there is no doubt that the inactivation is delayed or-under some circumstances-even impossible. Consequently, the cytosolic Ca concentration in skeletal muscle cells will increase and induce uncontrolled muscle activity. The recommendation is given to breed out this mutation for elimination of a major reason of the porcine stress syndrome and PSE.

Animals↗
PubMed1997

Analysis of metabolites--a new approach to bioequivalence studies of spironolactone formulations.

The aldosterone antagonist spironolactone undergoes extensive and complex biotransformation. For investigation of bioequivalence of 2 oral spironolactone formulations, Spironolacton 50 Heumann and Aldactone 50, the pharmacokinetics and bioequivalence of the parent drug and 2 predominant active metabolites, canrenone and 7 alpha-thiomethylspirolactone, were determined in a 2-way crossover study in 24 young healthy male volunteers after multiple oral dosing of 100 mg once daily. Plasma samples were measured by a newly developed HPLC assay and individual pharmacokinetic parameters of the 3 compounds were calculated by use of noncompartmental techniques. Statistical analysis was performed by ANOVA and nonparametric methods. Spironolactone was rapidly cleared from plasma. Therefore, only Css,max and tss,max were determined. Concerning Css,max bioequivalence was found with 90% classical shortest confidence interval ranging from 80.7-112.4%. The intrasubject variability for Css,max was determined to be 28.1%. Higher and persisting concentrations were observed for the metabolites. For canrenone 90% classical shortest confidence intervals were calculated as 95.4-105.0% for AUCss,tau, as 92.9-105.8% for Css,max, and as 89.1-106.3% for peak trough fluctuation (PTF). In the case of 7 alpha-thiomethylspirolactone the values were 84.2-103.0% for AUCss,tau, 77.0-98.6% for Css,max, and 85.0-100.4% for PTF. For tss,max nonparametric 90% confidence intervals were determined as 0.00 to 1.50 h for spironolactone and canrenone and as -0.50 to 1.00 h for 7 alpha-thiomethylspirolactone. The intraindividual variability was below 30% for all pharmacokinetic parameters in the case of the metabolites. Thus, bioequivalence of the test and the reference formulation can be concluded. The study suggests the inclusion of parent compound and metabolites for bioequivalence testing of spironolactone formulations. Intraindividual subject variability was clearly diminished by investigating bioequivalence under steady-state conditions.

Administration, Oral↗
PubMed1996

Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen.

Oxytocin (OT) has been shown to be the dominant peptide of the neurohypophysial family expressed by thymic epithelial and nurse cells (TEC/TNC) in various species. Thymic OT is not secreted but, after translocation of a hybrid neurophysin/MHC class I protein, is integrated within the plasma membrane of TEC, thus allowing its presentation to pre-T cells. In order to further demonstrate that thymic OT behaves like a membrane antigen, we assessed the effect of mAbs to OT on cytokine productions by cultures enriched in human TEC. 75-85% pure TEC cultures were prepared from human thymic fragments. Using immunofluorescence and confocal microscopy, ir-OT, ir-interleukin-1 beta (IL-1 beta), ir-interleukin-6 (IL-6) and ir-leukemia inhibitory factor (LIF) could be detected in these TEC cultures. ir-OT was restricted to TEC, while some ir-IL-6 and ir-LIF were also seen in occasional fibroblasts. In basal conditions, ir-IL-6 and ir-LIF (but not ir-OT and ir-IL-1 beta) were detected in the supernatants of human TEC cultures. MAbs to OT induced a marked increase of ir-IL-6 and ir-LIF secretion in TEC cultures. No significant effect was observed using mAbs against vasopressin, mouse immunoglobulins, or control ascitic fluid controls. These data show that OT is fully processed and recognized by specific mAbs at the outer surface of TEC plasma membrane. They further support that thymic OT behaves as the self-antigen of the neurohypophysial family.

Antibodies, Monoclonal↗
PubMed1996

Characterization of Na+/H+ exchange in sheep rumen epithelial cells kept in primary culture.

The study aimed at testing whether Na+/H+ exchange activity is maintained during isolation and cultivation of rumen epithelial cells (REC) and whether Na+/H+ exchange is altered during proliferation and differentiation. REC were isolated from sheep rumen epithelium by fractional trypsinization and further cultivated for up to 21 days. Characteristics of Na+ uptake into cultured REC were the same as previously described for the Na+/H+ exchange in the intact rumen epithelium. Na+ uptake was increased by intracellular acidification and was inhibited by high doses of amiloride. Amiloride inhibited 3H-thymidine incorporation into REC at concentrations similar to those found for the inhibition of Na+ uptake. Fetal calf serum, a growth factor, stimulated amiloride-sensitive Na+ uptake. We therefore conclude that cultured rumen epithelial cells express Na+/H+ exchange and that the activity of the exchange is at least correlated to the intensity of proliferation.

Amiloride↗
PubMed1996

Effects of potassium on magnesium transport across rumen epithelium.

Increasing ruminal K concentration impairs active Mg transport across the forestomach epithelium of ruminants. We used Ussing chamber and microelectrode techniques to test the hypothesis that high mucosal K decreases the driving force for Mg2+ uptake by depolarizing the apical membrane. Serosal Ba enhanced net 42K secretion. Under open-circuit conditions, rumen epithelial cells showed an apical membrane potential (Va) of -67.3 +/- 1.5 mV. An increase in mucosal K concentration depolarized Va and decreased mucosal-to-serosal 28 Mg flux (Jm-->sMg). An increase in the transepithelial potential difference (Vt) depolarized Va, greatly decreased Jm-->sMg, and slightly increased Mg serosal-to-mucosal flux (Js-->mMg). Jm-->sMg exhibited an electrogenic and an electroneutral component. Mucosal verapamil depolarized Va and reduced Jm-->sMg, without affecting Js-->mMg. The study shows that rumen epithelial cells exhibit apical and basolateral K conductances and that transcellular Mg absorption has a distinct electrogenic component. This supports the assumption that a change in Va represents the link between increased ruminal K concentration and decreased Mg absorption. The results are discussed with regard to the development of hypomagnesemia in ruminants.

Animals↗
PubMed1996

Development and evolutionary aspects of thymic T cell education to neuroendocrine self.

Thymic epithelial cells, including nurse cells (TECs/TNCs), from various species synthesize neuroendocrine-related precursors belonging to neurohypophysial, tachykinin and insulin hormone families. The thymic repertoire of neuroendocrine-related polypeptides illustrates at the molecular level the paradoxical role of the thymus in both T cell positive and negative selection. On the one hand, these precursors are a source of signals which interact with neuroendocrine-type receptors expressed by target pre-T cells according to the cryptocrine type of cell-to-cell signaling. On the other hand, the same precursors constitute a source of self-antigens which are presented to pre-T cells by the thymic major histocompatibility complex system. Basically, the model of thymic T cell education to neuroendocrine self was established by the identification in TECs/TNCs of immunoreactive (ir) oxytocin as the self-antigen of the neurohypophysial family. Nevertheless, through the expression in TECs/TNCs of ir-neurokinin A and ir-insulin-like growth factor-II, the model also applies to the tachykinin and insulin hormone families.

Animals↗
PubMed1996

The effects of a new low-dose combined oral contraceptive containing levonorgestrel on ovarian activity.

OBJECTIVE: The study was designed to evaluate the effects of a new low-dose monophasic combined oral contraceptive (100 micrograms levonorgestrel/20 micrograms ethinylestradiol) on ovarian activity. METHOD: This was an open-label study in 15 healthy female volunteers. After an ovulatory pretreatment cycle, subjects were treated for three consecutive cycles. RESULTS: Out of 15 healthy females with an ovulatory pretreatment cycle, 13 completed the study and two dropped out. In ten females, various degrees of ovarian activity were characterized, mainly in the second and third treatment cycle. In eight cases follicle-like structures either persisted or developed throughout the pill-free interval, growing up to luteinized unruptured follicles or cyst-like structures that reduced their size or disappeared in the following treatment cycle. CONCLUSION: Ovarian follicular activity was significantly suppressed during treatment with levonorgestrel 100 micrograms/ethinylestradiol 20 micrograms. Similarly, endogenous ovarian steroid production was almost uniformly decreased. A 'dissociation' of ovarian and endometrial development was also seen during this therapy.

Adolescent↗